This investigation is concerned with the structure, distribution, and metabolism of mucopolysaccharides (glycosaminoglycans) in nervous tissue. Histochemical studies have indicated the presence of mucopolysaccharides in the neuronal cytoplasm, at the nodes of Ranvier, and in the extracellular space and synaptic cleft in brain, and these findings are supported by the chemical isolation of hyaluronic acid, chondroitin sulfate and heparan sulfate from brain, spinal cord, and peripheral nerve. We are investigating certain aspects of the structure and distribution of these mucopolysaccharides in nerve tissue, such as the nature of the carbohydrate-protein linkages and the location of sulfate in heparan sulfate and the non-uronic acid-containing glycoproteins of brain. This study will also consider the metabolism of mucopolysaccharides in vivo, in both whole brain and in subcellular fractions. When appropriate, we will simultaneously investigate the properties of the mucopolysaccharides and of other types of glycoproteins in nervous tissue. The information obtained from these studies may be of value for our understanding of the factors which restrict the entry of drugs and other substances into the central nervous system, as well as the mechanisms of axonal and synaptic transmission of the nerve impulse, and the etiology of those forms of mental retardation which are associated with disturbances of mucopolysaccharide and glycoprotein metabolism.